The major goal of this project is to study the interaction between irradiation to specific organs and the pharmacology and toxicology of common chemotherapeutic drugs. Such a study is needed because of the increased use of combined radiation and chemotherapy and the paucity of information on the interactions between these therapeutic modalities. Experiments will be performed on patients where standard clinical protocols include a drug under study and local irradiation and where the protocol can permit pharmacokinetic and toxicologic monitoring. Rodents will be used for other studies. In all experiments irradiation will be delivered in standard fractionated doses. Specific Aims are: 1. To study the effect of hepatic irradiation on bile flow and the pharmacokinetics and toxicity of methotrexate, vincristine and adriamycin. 2. To study the effect of renal irradiation on renal function and the pharmacokinetics and toxicity of methotrexate. 3. To study the effects of cranial irradiation on the distribution and clearance of methotrexate and vincristine in the brain and/or cerebrospinal fluid. 4. To study the effect of chronic administration of methotrexate on the hepatic and renal toxicity of local irradiation.